Depressed? Appetite gone strange? Maybe the two are both down to leptin.© Punchstock

The appetite-control hormone leptin staves off symptoms of stress in rats, and might lead to new ways to fight human depression, say researchers in the United States.

Leptin is famed for controlling our weight and appetite. But the hormone, which is released by fat cells and gives the brain a reading of our fat stores, is also thought to act in brain areas involved in emotion.

To explore this link, Xin-Yun Lu and her colleagues at the University of Texas Health Science Center in San Antonio stressed rats by, for example, separating them from other animals. The rats' leptin levels plunged at the same time that they showed behavioural changes such as losing interest in a sugary drink, the kind of apathy that is often associated with human depression.

The team found that injections of leptin into otherwise healthy animals were as good as at least one known treatment in a test widely used to screen for new antidepressants. In this test, the researchers showed that leptin could help the animals to evade depression-induced behaviour when forced to swim.

The results, which the team report in the Proceedings of the National Academy of Sciences¹, are sure to trigger interest in those working on alternative therapies for depression. Many patients do not respond to existing treatments and doctors are keen to find more.

But they caution that much more work is needed before leptin becomes a candidate treatment for the blues. Because the hormone also exerts effects on appetite, reproduction and the immune system, medical researchers would probably need to find molecules that can specifically mimic leptin's anti-depressant effects on the brain without causing unwanted side effects.

It also isn't clear how well leptin's effect in animals is mirrored in people. The findings do fit with a few small studies suggesting that leptin levels are altered in people with depression. "It's very, very interesting," says Giovanni Cizza, who studies hormones and depression at the National Institute for Diabetes and Digestive and Kidney Disease in Bethesda, Maryland. But, he adds, "Depression is a very human phenomenon, so I take it with a grain of salt."

Fat chance

Leptin shot to fame in the mid 1990s when scientists discovered that a strain of immensely fat mice that eat voraciously lack a working copy of the gene. They found that leptin injections could help the mice to shed weight, raising the prospect that the hormone might be a miraculous fat fighter for the obese.

That hope was dealt a blow when leptin failed to fight flab for most people in clinical trials. Since then, scientists have realized that obese people often have high levels of leptin and seem to have become resistant to its effects. And now they know that the hormone has a host of other roles in the body too.

The new study raises questions about the link between appetite and mood. Many depressed patients lose weight and their interest in eating; a minority start to eat more. Experts say that low levels of leptin could conceivably fuel both depression and changes in appetite.

Lu and other researchers acknowledge that many factors, including the availability of tempting food and associations between eating and comfort, influence what and how much we consume. "It's affected by many, many things," says Cizza. "But leptin is a big player." 

• References

  1. Lu X. Y., et al. Proc. Natl Acad. Sci., published online /doi/10.1073/pnas.050890110 (2006).